I. Field of the Invention
The present invention relates generally to the fields of oncology and molecular biology. More particularly, it concerns targeting of cancer cells expressing DF3/MUC1 antigens using a DF3/MUC1-regulated viral expression construct.
II. Description of Related Art
Recombinant adenoviruses have been used as highly efficient vectors for in vitro and in vivo gene transfer. Adenovirus-mediated gene transduction has been achieved in a broad spectrum of eukaryotic cells, and is independent of cell replication (Haj-Ahmad et al., 1986; Bett et al., 1994). In addition, E1 gene-deleted, replication-defective adenoviruses can accommodate large DNA inserts (Haj-Ahmad et al., 1986; Bett et al., 1994).
However, limitations of this vector system for cancer therapy have resulted in the non-selective delivery of therapeutic genes to both normal cells and tumor cells. Moreover, replication-defective adenoviruses are limited by their inability to infect and then spread to neighboring tumor cells. Strategies to circumvent these limitations involve the use of promoters or enhancers that are specific to or selective for tumor tissue in order to direct replication of the adenovirus in the desired target cells (Heise et al. 2000). In this context, the minimal promoter/enhancer from the prostate-specific antigen (PSA) gene has been used to drive E1A expression and thereby create an adenovirus, designated CN706, that selectively replicates in PSA-positive cells (Rodriguez et al., 1997). A similar strategy using the albumin promoter has been used to develop a herpes simplex virus that selectively replicates in hepatoma cells (Miyatake et al. 1999). Other tissue specific promoters include carcinoembryonic antigen (CEA) and alpha-feto protein (AFP).
Tissue specific promoters have also been used to drive the expression of therapeutic genes. For example PSMA, a type 2 membrane protein expressed in the prostate, is a useful target for prostate cancer therapy. The PSMA construct has been used to drive the suicide gene cytosine deaminase (Uchida et al., 2001). Another group has directed gene therapy specifically to vascular wall for treating vascular disease and cancer using the PPE-1 promoter (Varda-Bloom et al., 2001). The various types of tissue specific promoters/enhancers are described elsewhere in the specification.
In spite of these efforts, there remains a need in the art to construct vectors that can exploit the benefits of tissue specific gene expression in cancer cells.